A polymer support is a polymer onto which a functional molecule, such as a reagent or catalyst, is chemically bound, immobilized, dispersed, or associated. A polymer support is usually a network polymer, typically prepared in bead form by suspension polymerization or isolated from a natural source. The location of active sites introduced into a polymer support depends on the type of polymer support. In a swollen-gel-bead polymer support the active sites are distributed uniformly throughout the beads, whereas in a macroporous-bead polymer support they are predominantly on the internal surfaces of the macropores. Natural polymers could potentially have either attribute.
In order to separate the active reagent or catalyst away from the polymer, often referred to as the polymer backbone, a linker may be introduced. The linker may be in the form of a ligand and is typically introduced as a bifunctional moiety or molecule which is reactive to the polymer on one side and reactive to the supported functional molecule, such as a reagent, catalyst or protein, on the other side. The linker could also, for example, be a chelate where it is superceded by a non-covalent/ionic interaction with a metal. A linker thus minimises the potential for non-selective interaction between the polymer backbone and the reactants in the solution in which it is suspended.
In this specification “linker” shall have its widest meaning and shall include a molecule or compound which acts to couple or bond a functional molecule to a polymer.
As will be apparent, one use for polymer supports is in the manufacture of catalysts where catalytic material is supported on a polymer.
Palladium-catalysed cross coupling reactions of organo-halides with olefins and organo-boronic acids for carbon-carbon bond formation are extremely useful to the chemical industry and in research. Since their discovery they have evolved into a general technique in preparing biologically active functionalised biphenyls which are important intermediates or products in drug discovery, pharmaceuticals and agricultural compounds.
Historically, palladium complexes such as [Pd(OAc)2] and [Pd(PPh3)Cl2] have been widely used as homogenous catalyst systems in cross coupling reactions. However, these homogenous catalytic systems suffer from problems associated with the separation and recovery of the active catalyst as well as instability at high temperatures. These drawbacks have so far limited the industrial exploitation. From the perspective of process development, homogenous catalysts require expensive phosphine ligands (to generate the active catalyst) which are often not available in bulk. Metal contamination of the products is inevitable when using homogenous catalysts. This is an undesirable result, especially in the pharmaceutical industry. There is therefore a need to develop improved and practical strategies for recycling active catalysts for economic and environmental stewardship reasons.
Most of the problems related to homogenous catalysts can be solved by immobilising the catalyst or catalyst precursor on polymer supports with good solvation attributes. Supporting transition metal catalysts on insoluble or soluble polymer supports can, for example, improve the stability without compromise in the activity and selectivity of the catalyst. Supported catalysts also allow simplified recovery and reuse of the catalyst as well as physical separation of the active site, thus minimising catalyst self-destruction.
Due to the inherent advantages of heterogenising homogenous catalysts through immobilisation on solid supports, a great deal of effort has been devoted to these developments. However, the majority of these reported catalysts based on synthetic organic polymer supports, such as polystyrene, poly(ethylene) glycol and the like, and inorganic supports, such as silica, alumina and other metal oxides, including commercial supported catalyst such as [(PPh3)4Pd]-cross-linked polystyrene-bound and Pd0 on alumina. Recent efforts in the development of environmentally friendly, sustainable chemistry have led to the use of biopolymers as catalyst supports. Biopolymers are readily available in nature and can be used as suitable supports for many reagents and catalysts, thus offering the advantages of being renewable, biodegradable and non-toxic. Biopolymers such as cellulose, gelatine and starch have been investigated as catalyst supports. In recent years, the alternative polymer chemistry and functionalisation potential of chitosan have also been investigated.
Chitin is the second most abundant natural biopolymer in the world, behind only cellulose. It is a heterogeneous polysaccharide that consists of beta-1,4-linked N-acetylglucosamine residues that are arranged in antiparallel (alpha), parallel (beta), or mixed (gamma) strands, with the alpha configuration being the most abundant. It is also the most abundant naturally occurring polysaccharide that contains amino sugars. This abundance, combined with the specific chemistry of its derivative, chitosan, provides for an array of potential applications. Chitin and chitosan have already found applications in diverse products that have reached the market. The material is widely available globally and comes in a variety of grades and from numerous sources.
Chitosan is produced by deacetylation of the abundant biopolymer chitin, a key constituent of the exoskeletons of crustaceans and the cell walls of algae. It has been shown to exhibit interesting biopesticidal, antifungal and anti-cancer properties and has been used successfully in food and water treatment.
Chitosan can be readily transformed into films or fibres and has found applications as adsorbents for metals, in medicine and in drug delivery. Its chirality, variable degree of solubility in many organic solvents after modification and capability of being cast into films and fibres from dilute acid makes chitosan an excellent candidate as a support for catalysts. Several catalytic systems using chitosan as a support are in fact known. Functionalisation of chitosan to provide coordination sites has been carried out and this has provided catalysts for oxidation, cyclopropanation of olefins, Suzuki and Heck cross coupling reactions.
Due to the poor aqueous solubility of natural chitin and more so, chitosan, it is desirable to find a water soluble derivative of chitosan. Numerous strategies have been proposed for conjugating polar groups to the 6-hydroxy and or the 2-amino functional groups of chitosan. Satoh et al (T. Satoh, H. Kano, M. Nakatani, N. Sakairi, S. Shinkai and T. Nagasaki, Carbohydr. Res., 2006, 341, 2406-2413) first reported the preparation of modified chitosan (6-deoxy 6-amino chitosan), which was used as a gene carrier. The reported procedure involved the synthesis of a 2-amino protected chitosan in the form of N-phthaloyl-chitosan. Having protected the amino group, the 6-hydroxy group of chitosan could selectively be converted to the 6-chloro, 6-bromo or 6-iodomethylene polymer. Substitution of the halogen with an azido group, followed by reduction thereof, gave the 6-deoxy 6-amino chitosan.
It is, however, impractical to scale up the polymer synthesis using the above prior art route since it requires relatively large reagent mass transfers and results in poor product quality. Other than in its above role in gene transfer, no further applications for 6-amino 6-deoxy chitosan have been proposed.